Trauma is a leading health problem in the United States today. Trauma is the number one killer of young adults and it ranks third overall, following heart disease and cancer. For every American who dies as a result of trauma, there are three Americans permanently disabled (500,000 permanent disabilities/year).
Approximately 50% of deaths from trauma occur within seconds of the injury. Trauma prevention is the only way to alter deaths which occur immediately following injury. A second peak in deaths occurs within two or three hours after the trauma and is dependent upon available intervention and treatment of the life-threatening aspects ofthe injury. The third peak occurs days or even weeks following the injury and is usually caused by sepsis and/or multiple organ failure. Sepsis may be defined as the presence of bacterial infection. Septicemia continues to be a problem in the critically ill, surgical or traumatized patient. Death secondary to systemic sepsis is not uncommon and may occur two to four weeks after the initial injury.
Severe injury or trauma, including surgery, is associated with loss of the body's nutrient stores due both to the injury itself and the resulting catabolic state. For optimal recovery, critically ill patients need proper nutritional intake. Lack of it can result in malnutrition-associated complications, including prolonged negative nitrogen balance, depletion of somatic and visceral protein levels, immune incompetence, increased risk of infection, and other complications associated with morbidity and mortality. A primary objective of nutritional support for the traumatized person is to replace or maintain the body's normal level of nutrients by providing adequate energy substrates, protein, and other nutrients essential for tissue repair and recovery.
While nutrients may be provided by either parenteral or enteral routes, clinicians are making greater efforts to use the enteral route in light of research showing that enteral feeding confers certain physiologic benefits not seen with parenteral feeding. Published studies have reported that early enteral feeding provides energy and nutrients essential for optimal healing and immunocompetence, helps maintain the gut mucosal integrity, and may blunt catabolic effects and normalize blood glucose levels. Certain nutrients have effects on the gastrointestinal tract and immune system that go beyond the provision of nutrition. For example, beta-carotene, lactalbumin, and arginine are known to have specific physiologic benefits that are especially important for trauma and surgical patients.
Severe injury and major surgery causes abrupt changes in body metabolism. These changes vary with the type of trauma, previous health status, and medical care. Hormonally mediated hypermetabolism, catabolism, elevated basal metabolic rate and nitrogen excretion, altered fluid and electrolyte balance, synthesis of acute phase proteins, inflammation, and immunosuppression are often observed after severe injury, major surgery, or critical illness. The gastrointestinal tract is frequently affected by trauma or surgery. Blood flow may be reduced by hemorrhage, and the resulting loss of oxygen and nutrients may damage mucosal cells. However, the presence of intraluminal nutrients helps protect the gastrointestinal tract.
Epithelial cells such as those lining the gut are an important barrier against bacterial infection. The importance of the "first line of defense" provided by epithelial cells is evident, for example, in the patient suffering from a serious burn who is at risk of infection due to the destruction of skin.
Appropriate enteral nutrition following injury may minimize malnutrition, provide nutrients to the immune system and maintain the gut epithelial which acts as a barrier to translocation of bacteria. This may help prevent the development of sepsis. Malnutrition may compromise the immune system and contribute to the high incidence of septic complications. It has been reported that cell-mediated immunity is reduced in proportion to thelevel ofmalnutrition of the critically ill patient.
Following severe trauma and major surgery, gastrointestinal disturbances such as diarrhea, abdominal bloating and aspiration, have been associated with enteral feeding. These disturbances are caused by complex interactions between the trauma response, antibiotic and drug therapy as well as the enteral feeding. If at all possible, enteral feeding is advised to maintain mucosal integrity. The well-known "paralytic ileus" is usually confined to the stomach. The small intestine may retain motility and often enteral nutritional through the small intestine can be used successfully. It is essential that the proper administration of nutrients, including water, be monitored in order to prevent a further deterioration of the nutrient status of the critically ill patient. For those patients who are volume intolerant it is difficult to meet their caloric requirements with standard enteral nutritional products.
Both anabolic and catabolic processes are accelerated following severe trauma, although catabolism predominates. This response allows muscle breakdown to occur in order to provide amino acids for synthesis of proteins involved in immunological response and tissue repair. However, some mobilization of protein and calcium can be attributed to bed rest. Disuse atrophy contributes to the muscle wasting and negative nitrogen balance frequently observed in the trauma patient.
The catabolism of trauma occurs as a mechanism to provide substrate through the breakdown of muscle tissue. Hypermetabolism also occurs; however, it is difficult to meet the caloric needs of the patient. Dietary protein may be utilized as an energy substrate which necessitates the excretion of nitrogenous products. Catabolism following trauma or major surgery may be obligatory and it is uncertain whether it could be altered by the intake of large doses of protein. Overall negative nitrogen balance observed in traumatized and septic patients may be attributed to an inadequate caloric intake, rather than an insufficient protein intake.
The nutritional support of trauma and surgery patients has been extensively investigated in the prior art.
There are commercially available nutritional products intended for trauma or surgery patients. IMPACT.RTM. is a ready-to-use enteral formula which is distributed by SANDOZ NUTRITION, Minneapolis, Minn., U.S.A.. IMPACT.RTM. contains a much greater level of L-arginine than the product of the present invention, and has a lower caloric density than the product of the present invention. IMMUN-AID.TM., a nutritional product for immunocompromised patients, is distributed by McGaw, Inc. of Irvine, Calif., U.S.A.. IMMUN-AID.TM. is distributed in powdered form and contains intact protein and amino acids. OSMOLITE.RTM. HN distributed by Ross Laboratories of Columbus, Ohio, U.S.A. is not specifically formulated for trauma or surgery patients but has often been employed for this purpose.
U.S. Pat. No. 4,042,688 relates to a nutritional supplement, taken for example in tablet form, which contains predigested protein in the form of a gelatin hydrolysate. The gelatin hydrolysate used in that invention is made by hydrolyzing animal collagen, preferably a collagen derived from the skin of pork bellies, by means of enzymatic hydrolysis, and then spray drying the gelating solution. The predigested protein employed in the present invention is a higher quality protein than that derived from gelatin, and the nutritional product of the present invention provides a balanced diet rather than being a diet supplement.
U.S. Pat. No. 4,438,144 teaches a nutritional composition that may be provided either enterally or parenterally, preferably parenterally, wherein the amino acids comprise from about 70 to 100% valine, isoleucine and leucine, collectively. However, the nutritional product of the present invention is formulated to provide a balanced diet and does not contain such high concentrations of these specific amino acids.
U.S. Pat. No. 4,920,098 relates to a method of providing nutritional support as cardiac therapy. This therapy regimen may be administered either parenterally or enterally. The nutritional product is formulated to provide energy and protein substrates that are especially beneficial to cardiac tissues. Although the caloric distribution taught in this patent is similar to that of the nutritional product disclosed herein, the new product contains a much different protein system and is formulated for a different patient population.
U.S. Pat. No. 5,053,387 teaches a nutritional composition containing intact protein, preferably whey, and contains arginine in the amount of about 1-3% of the total energy intake. In a preferred embodiment the lipid consists of a mixture of equal amounts of fish oil and safflower oil. The caloric distribution of the composition taught in this patent is substantially different from that of the nutritional product of the present invention.
Published Australian Patent Application 36917/84 relates to an amino acid solution that may be provided either enterally or parenterally to a patient, but does not teach a composition for providing a balanced diet as in the present invention.
Published European Patent Application No. 0 367 724 teaches a nutritional composition containing intact protein, arginine and marine oil. It has a caloric density which is substantially lower than that of the nutritional product of the present invention.
Published PCT application WO 91/09524 relates to a method of treating a patient having an impaired immune response due to trauma or surgery. The method involves providing the patient with about 15 to 35 grams of arginine per day. Nutritional formulations for providing the arginine are disclosed in this PCT application. Arginine is provided at a level of about 6.9 to 11.1 grams per 1,500 kcal by the nutritional product of the present invention (with 1,5000 kcal per day being the nutrient base of the new product).
European Patent Application 0 312 612 teaches a "nutritive emulsion" containing an "amino acid preparation", a lipid and water. The caloric density of the "nutritive emulsion" is adjusted to a desired level by the amount of sugar in the emulsion.
Japanese Patent Application Sho 61-192245 teaches that cows milk protein should be supplemented by arginino at a level of 3.5-7.0% of the amino acids in the product for a nutritional product for infants. The nutritional product of the present invention has an amino acid profile containing 9.0 to 13.8% arginine.